Emerging evidence for astrocyte dysfunction in schizophrenia

Abstract

Schizophrenia is a complex, chronic mental health disorder whose heterogeneous genetic and neurobiological background influences early brain development, and whose precise etiology is still poorly understood. Schizophrenia is not characterized by gross brain pathology, but involves subtle pathological changes in neuronal populations and glial cells. Among the latter, astrocytes critically contribute to the regulation of early neurodevelopmental processes, and any dysfunctions in their morphological and functional maturation may lead to aberrant neurodevelopmental processes involved in the pathogenesis of schizophrenia, such as mitochondrial biogenesis, synaptogenesis, and glutamatergic and dopaminergic transmission. Studies of the mechanisms regulating astrocyte maturation may therefore improve our understanding of the cellular and molecular mechanisms underlying the pathogenesis of schizophrenia.

Keywords: astrocytes; dopamine; gliotransmitter; mitochondria; schizophrenia.

FIGURE 1

Schematic of prominent processes occurring during different periods of mouse fetal and postnatal brain development. Developmental processes as occur in astrocytes (green, above), and neurons (blue, below) are shown.

FIGURE 2

Astrocytes in normal brain and in brain affected of schizophrenia. It is now widely recognized that astrocytes play crucial roles both during postnatal development and in the adulthood because they are necessary for development of neuronal circuits and for the maintenance of multiple homeostatic functions such as the buffering of extracellular ions or the modulation of synaptic activity. Several recent studies have point out that schizophrenia induces molecular changes in astrocytes (including modifications in the rate of mitochondrial biogenesis) that can results in an aberrant postnatal maturation of astrocytes. As the formation and maturation of neuronal circuits occurs concomitantly to astrocytes maturation, it is evident that any dysfunctions in their morphological and functional maturation may have a direct impact to the formation of neuronal circuits that ultimately may lead to aberrant neurodevelopmental processes involved in the pathogenesis of schizophrenia.